Ortega, Maria JParra-Torrejon, BelenCano-Cano, FatimaGomez-Jaramillo, LauraGonzalez-Montelongo, M CarmenZubia, Eva2023-05-032023-05-032022-05-07Ortega MJ, Parra-Torrejón B, Cano-Cano F, Gómez-Jaramillo L, González-Montelongo MC, Zubía E. Synthesis and Antioxidant/Anti-Inflammatory Activity of 3-Arylphthalides. Pharmaceuticals (Basel). 2022 May 10;15(5):5881424-8247http://hdl.handle.net/10668/21534Phthalides are a group of compounds with relevant biological activities in different areas such as cytotoxicity, anti-stroke activity, neuroprotection, and inflammation, among others. In this study we designed and synthesized a series of 3-arylphthalide derivatives in order to identify their antioxidant and anti-inflammatory activities. The synthetic methodology was established in terms of atom and step economy through a dehydrative coupling reaction between 3-hydroxyphthalide and different properly functionalized arene rings. The evaluation of the antioxidant activity was performed by the ABTS assay and for the anti-inflammatory activity the inhibition of LPS-induced nitric oxide (NO) production in microglial cells Bv.2 and macrophage cells RAW 264.7 was measured. The synthesized compound 3-(2,4-dihydroxyphenyl)phthalide (5a) showed better antioxidant activity than the Trolox standard and caused strong inhibition of NO production in LPS-stimulated Bv.2 and RAW 264.7 cells. In addition, compound 5a reduced the expression of the pro-inflammatory cytokines Il1b and Il6 in RAW 264.7 cells. These results, which are the first account of the anti-inflammatory activity of 3-arylphthalides, suggest that compound 5a could be a promising candidate for more advanced anti-inflammatory studies.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/3-arylphthalidesAnti-inflammatoryAntioxidantCytokinesDehydrative coupling reactionPhthalidesresearch article35631414open access10.3390/ph15050588PMC9144619https://www.mdpi.com/1424-8247/15/5/588/pdf?version=1652258409https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144619/pdf